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Colon interposition counts among the most common techniques for reconstruction of the intestinal passage after esophagectomy. Data on metachronous mucosal pathologies such as adenoma and adenocarcinoma in the literature are weak, and no systematic reviews or meta-analyses exist. The planned analysis aims to assess the frequency of polyp growth and/or development of adenocarcinoma in adult colon interposition patients. Therefore, a systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines in the following databases: Medline/PubMed, Science Direct, Cochrane database for randomized trials (CENTRAL), Bayerische Staatsbibliothek Munchen, Library of the University Hospital Regensburg, Germany, Library of the Charite, University Hospital Berlin. All studies (randomized and non-randomized, case series, case reports) reporting on adult patients with colon interposition for reconstruction of the intestinal passage after esophagectomy for benign (e. g., Boerhaave syndrome, trauma, corrosive injury) or malignant reasons (esophageal cancer) are eligible for data analysis. Randomized and non-randomized studies will be included into the qualitative analysis. The review protocol and the systematic review itself are constructed in accordance with the PRISMA statement and the recommendations of the Cochrane Handbook for systematic reviews. This systematic review protocol is registered with the PROSPERO International Prospective Register of Systematic Reviews ( http://www.crd.york.ac.uk/prospero ) as CRD42017082144.